Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.

Overview

This study aims to assess the effectiveness and cost-effectiveness of rectal swab culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral ciprofloxacin (control group), while the other half will receive rectal culture-guided oral antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis, comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative oral antibiotic based on the culture results will be prescribed (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin).

The investigators hypothesise that the targeted prophylaxis group (intervention group) will have a lower rate of post-biopsy infectious complications compared to the control group.

Full Title of Study: “The Effect of Rectal Swab Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy on Infectious Complications and Cost of Care: A Randomized Controlled Trial in the Netherlands.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2020

Detailed Description

Several classes of antibiotics are proven effective for prophylaxis during transrectal prostate biopsy, reducing infectious complications to less than 1% in case of susceptible rectal flora. Ciprofloxacin has been best studied and is recommended as first choice prophylaxis in urology guidelines. However, due to increasing fluoroquinolone resistance in gram negative bacilli (currently more than 20% in E.coli), a significant increase up to 6% in infectious complications after transrectal prostate biopsy was recently noticed. Antibiotic treatment of these infections and hospitalization may account for increased health care associated costs and will contribute to the further development of antibiotic resistance.

Besides, in urology guidelines no clear recommendations are made on the duration of prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin schedules are used, of which 2 to 3 day regimens are most common. Prolonged duration of prophylaxis during prostate biopsy is not proven to be more effective than a 1-day regimen, but it is more likely to select more fluoroquinolone (FQ) resistance.

This study aims to assess the effectiveness and cost-effectiveness of rectal culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Also, duration of antibiotic prophylaxis will be minimized to 24 hours, thereby controlling further development of resistant bacteria.

The culture method used in this study with four phenotypic screening agars to support the choice of one of the oral prophylactic antibiotics is innovative. Culture results become available rapidly, within 48 hours, the method is simple, relatively inexpensive, as it does not need full susceptibility testing of separate colonies, and useful in daily practice.

Interventions

  • Drug: Ciprofloxacin
    • see study arms.
  • Drug: Trimethoprim/Sulfamethoxazole
    • see study arms.
  • Drug: Fosfomycin
    • see study arms.
  • Drug: Pivmecillinam/augmentin
    • see study arms.

Arms, Groups and Cohorts

  • Experimental: Targeted antimicrobial prophylaxis
    • Men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy (equal to the active comparator arm), and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative oral antibiotics, based on culture results, in the following order: trimethoprim/sulfamethoxazole (SXT) 960 mg orally 2 hours before and 12 hours after prostate biopsy, or fosfomycin 3 g orally 2 hours before prostate biopsy, or pivmecillinam/augmentin respectively 400 mg and 500/125 mg 2 hours before prostate biopsy followed by 2 days with three divided doses each day after prostate biopsy.
  • Active Comparator: Routine empirical prophylaxis
    • Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.

Clinical Trial Outcome Measures

Primary Measures

  • Any registered clinical infectious complication after prostate biopsy
    • Time Frame: within 7 days post-biopsy
    • Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis

Secondary Measures

  • Cost of care
    • Time Frame: within 30 days after prostate biopsy
    • Difference of costs between the intervention and the control group
  • Positive microbiological results
    • Time Frame: within 7 and 30 days after prostate biopsy
    • Urine or blood culture results
  • Any registered clinical infectious complication after prostate biopsy
    • Time Frame: within 7 and 30 days after prostate biopsy
    • Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis
  • Hospitalization after prostate biopsy
    • Time Frame: within 30 days after prostate biopsy
    • Any hospital admission, including ICU admission
  • Overall mortality
    • Time Frame: within 30 days after prostate biopsy
    • Mortality of any cause
  • Side effects of used antibiotics
    • Time Frame: within 30 days after prostate biopsy
    • All side effects mentioned in the Summary of Product Characteristics (SPC)
  • Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora
    • Time Frame: rectal swabs are taken 14 days before biopsy
    • Assessed through microbiological rectal swab cultures
  • Overall antibiotic use after prostate biopsy
    • Time Frame: within 30 days after prostate biopsy
    • Number of antibiotic prescriptions

Participating in This Clinical Trial

Inclusion Criteria

  • Subject is able and willing to sign the Informed Consent Form.
  • Subject undergoes a transrectal prostate biopsy as part of the standard care in the Radboudumc (Nijmegen), Canisius Wilhelmina hospital (Nijmegen) or Catharina hospital (Nijmegen) (because of suspicion of prostate cancer).

Exclusion Criteria

  • Inability to receive ciprofloxacin (e.g. documented history of sensitivity to medicinal products or excipients similar to those found in the antibiotic prophylaxis, relevant history or presence of cardiovascular disorders)
  • Inability to receive either co-trimoxazole, fosfomycin and pivmecillinam/augmentin prophylaxis for any reason (e.g. documented history of sensitivity to medicinal products or excipients similar to those found in the antibiotic prophylaxis)
  • Inability to understand the nature of the trial and the procedures required.
  • Individuals with an urinary tract infection or acute prostatitis within 14 days prior to intervention.
  • Individuals who receive antibiotics within 14 days before prostate biopsy.
  • Individuals who fail to send a rectum swab to the microbiology laboratory.
  • Individuals whose rectal swab shows no growth on a (growth) control MacConkey agar without antibiotics.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Radboud University
  • Collaborator
    • ZonMw: The Netherlands Organisation for Health Research and Development
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Heiman Wertheim, Prof. dr., Study Director, Radboud University
  • Overall Contact(s)
    • Eva Kolwijck, Dr., +31243614356, eva.kolwijck@radboudumc.nl

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